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- Coombes, D., et al.
(author)
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The basis for non-canonical ROK family function in the N-acetylmannosamine kinase from the pathogen Staphylococcus aureus
- 2020
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In: Journal of Biological Chemistry. - 0021-9258. ; 295:10, s. 3301-3315
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Journal article (peer-reviewed)abstract
- In environments where glucose is limited, some pathogenic bacteria metabolize host-derived sialic acid as a nutrient source. N-Acetylmannosamine kinase (NanK) is the second enzyme of the bacterial sialic acid import and degradation pathway and adds phosphate to N-acetylmannosamine using ATP to prime the molecule for future pathway reactions. Sequence alignments reveal that Gram-positive NanK enzymes belong to the Repressor, ORF, Kinase (ROK) family, but many lack the canonical Zn-binding motif expected for this function, and the sugar-binding EXGH motif is altered to EXGY. As a result, it is unclear how they perform this important reaction. Here, we study the Staphylococcus aureus NanK (SaNanK), which is the first characterization of a Gram-positive NanK. We report the kinetic activity of SaNanK along with the ligand?free, N-acetylmannosamine?bound and substrate analog GlcNAc?bound crystal structures (2.33, 2.20, and 2.20 ? resolution, respectively). These demonstrate, in combination with small-angle X-ray scattering, that SaNanK is a dimer that adopts a closed conformation upon substrate binding. Analysis of the EXGY motif reveals that the tyrosine binds to the N-acetyl group to select for the ?boat? conformation of N-acetylmannosamine. Moreover, SaNanK has a stacked arginine pair coordinated by negative residues critical for thermal stability and catalysis. These combined elements serve to constrain the active site and orient the substrate in lieu of Zn binding, representing a significant departure from canonical NanK binding. This characterization provides insight into differences in the ROK family and highlights a novel area for antimicrobial discovery to fight Gram-positive and S. aureus infections.
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- Setty, V., et al.
(author)
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Maximizing the number of satisfied subscribers in pub/sub systems under capacity constraints
- 2014
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In: Proceedings - IEEE INFOCOM. - 9781479933600 ; , s. 2580-2588
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Conference paper (peer-reviewed)abstract
- Publish/subscribe (pub/sub) is a popular communication paradigm in the design of large-scale distributed systems. A provider of a pub/sub service (whether centralized, peer-assisted, or based on a federated organization of cooperatively managed servers) commonly faces a fundamental challenge: given limited resources, how to maximize the satisfaction of subscribers? We provide, to the best of our knowledge, the first formal treatment of this problem by introducing two metrics that capture subscriber satisfaction in the presence of limited resources. This allows us to formulate matters as two new flavors of maximum coverage optimization problems. Unfortunately, both variants of the problem prove to be NP-hard. By subsequently providing formal approximation bounds and heuristics, we show, however, that efficient approximations can be attained. We validate our approach using real-world traces from Spotify and show that our solutions can be executed periodically in real-time in order to adapt to workload variations.
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- Setty, V., et al.
(author)
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The hidden pub/sub of spotify (Industry Article)
- 2013
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In: DEBS 2013 - Proceedings of the 7th ACM International Conference on Distributed Event-Based Systems. - New York, NY, USA : ACM. - 9781450317580 ; , s. 231-240
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Conference paper (peer-reviewed)abstract
- Spotify is a peer-assisted music streaming service that has gained worldwide popularity. Apart from providing instant access to over 20 million music tracks, Spotify also enhances its users' music experience by providing various features for social interaction. These are realized by a system using the widely-adopted pub/sub paradigm. In this paper we provide an interesting case study of a hybrid pub/sub system designed for real-time as well as offline notifications for Spo-tify users. We firstly describe a multitude of use cases where pub/sub is applied. Secondly, we study the design of its pub/sub system used for matching, disseminating and persisting billions of publications every day. Finally, we study pub/sub traffic collected from the production system, derive characterizations of the pub/sub workload, and show some interesting findings and trends.
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- Wells, Geoff J., et al.
(author)
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Hundreds of millions of people in the tropics need both wild harvests and other forms of economic development for their well-being
- 2024
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In: One Earth. - 2590-3330 .- 2590-3322. ; 7:2, s. 311-324
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Journal article (peer-reviewed)abstract
- Local access to “wild,” common-pool terrestrial and aquatic resources is being diminished by global resource demand and large-scale conservation interventions. Many theories suggest the well-being of wild harvesters can be supported through transitions to other livelihoods, improved infrastructure, and market access. However, new theories argue that such benefits may not always occur because they are context dependent and vary across dimensions of well-being. We test these theories by comparing how wild harvesting and other livelihoods have been associated with food security and life satisfaction in different contexts across ∼10,800 households in the tropics. Wild harvests coincided with high well-being in remote, asset-poor, and less-transformed landscapes. Yet, overall, well-being increased with electrical infrastructure, proximity to cities, and household capitals. This provides large-scale confirmation of the context dependence of nature’s contributions to people, and suggests a need to maintain local wild resource access while investing in equitable access to infrastructure, markets, and skills.
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